Relapse is one of the most problematic aspects in the treatment of alcoholism with the majority of abstinent alcoholics relapsing during their lifetime. Relapse is triggered by three general classes of stimuli: exposure to stress, alcohol, or alcohol-associated environmental cues. There is an increasing amount of evidence indicating that glutamate neurotransmission plays a critical role in cue-induced relapse-like behavior. The overall objective of this proposal is to use enzyme-based biosensor technology to monitor changes in extracellular glutamate during cue-induced reinstatement of alcohol-seeking behavior. These studies will employ our recently developed cue-induced reinstatement paradigm in rats with a history of intravenous ethanol self-administration. Specifically, this research proposal will monitor changes in extracellular glutamate in the basolateral amygdala (BLA) and nucleus accumbens core (NAcCo) during cue-induced reinstatement of ethanol-seeking behavior, and to determine if any observed changes in extracellular glutamate in these regions are specific for alcohol by performing similar experiments during cue-induced reinstatement of food-seeking behavior. Findings from these studies will reveal changes in glutamatergic transmission that occur during cue-induced relapse-like behaviors. While previous studies have shown that blockade of glutamatergic transmission can prevent reinstatement of drug-seeking behavior, few studies have examined specific changes in glutamate levels in discrete brain regions resulting from alcohol cues. Additionally, with the potential of revealing possible neural areas/substrates that are involved in alcohol relapse, these results will hopefully lead to improved therapies for the prevention of relapse to alcohol consumption elicited by alcohol-associated environmental cues.